The segment of the TOP-IMPLART accelerator up to 150 MeV has

been funded by Regione Lazio and is under realization at ENEA-

Frascati Center choose as a test site. The accelerator is based on

the 7 MeV injector consisting in a 3 MeV RFQ followed by a DTL

up to 7 MeV (PL-7ACCSYSHITACHI model) followed by a vertical

and an horizontal beam transport line matching the beam to the

following accelerating modules.

TOP-IMPLART LINEAR ACCELERATOR FOR PROTON THERAPY:

LAYOUT AND FIRST RADIOBIOLOGICAL RESULTS AT LOW ENERGYMaria Antonella Tabocchini1, Alessandro Ampollini2, Giulia Bazzano2, Francesca Marracino2, Concetta Ronsivalle2, Monia Vadrucci2, Maria Balduzzi3,

Clarice Patrono3, Claudia Snels3, Antonella Testa3, Pasqualino Anello1, Cinzia De Angelis1, Giuseppe Esposito1, Marco D’Andrea4, Lidia Strigari4

7 MeV7 MeV 150 MeV150 MeV35 MeV35 MeV 230MeV230MeV

Head-NeckTumors

Head-NeckTumors

In-vitro and in-vivoRadiobiology

In-vitro and in-vivoRadiobiology

In vitroRadiobiology

In vitroRadiobiology

18 MeV18 MeV Deep TumorDeep Tumor

The section of the accelerator up to 11.6 MeV module, is

already installed and has been tested. Additional modules

will be added to the injector leading proton energy to 30, 70

and 150 MeV in a step by step project. …..

The 7 MeV injector proton beam was used for radiobiology experiments

devoted to a biological characterization of the beams in terms of the cell

killing. A dedicated radiobiology vertical beam line has been implemented.

To this purpose, a 90° vertical bending magnet is placed in the middle of

the low energy beam transport line. In this way it is possible to select the

requested energy of protons impinging on the cells.

The first radiobiological experiments were carried out to characterize the proton beam. To this purpose, cell

killing experiments were conducted at the TOP-IMPLART vertical transport line on V79 and CHO cells. Irradiations

have been performed with protons extracted in air and impinging on the cells with energy of 5 MeV (incident

LET=7.7 keV/μm in MS20); the clonogenic survival was evaluated in the dose range 0.5-8 Gy.

90° magnet

Acknowledgements: Thanks are due to FILAS-Regione Lazio for funding the TOP-IMPLART Project, coordinated by L. Picardi, C.Marino (ENEA) and E. Cisbani (ISS), and to R.Cherubini (LNL-INFN) for his prime scientific support.

Sample holder Beam line

1Istituto Superiore di Sanita (ISS) and INFN-Gr.coll.Sanita (Italy), 2ENEA-Frascati, Rome (Italy), 3ENEA- Casaccia, Rome (Italy),

4Regina Elena National Cancer Institute, IFO, Rome (Italy)

INFN-LNL radiobiology irradiation setup (in air): single sample holder and set of sample holders placed on the revolving system remotely controlled during measurements.

The same sample holders especially designed for

proton irradiation at the LNL (Belli et al, Nucl Instr Meth

1987) have been used at the TOP-IMPLART during

irradiation of Chinese hamster cells with protons of 5

MeV, corresponding to an incident LET (in MS20

tissue) of 7.7 keV/µm. Gaf-Chromic EBT3 film have

shown a uniformity of 90% on the irradiated area.

Calibration curves Dose vs. netOD of the EBT3 films irradiaed at the LNL with 5MeV protons at the dose rate of 2.1 Gy/min

LAYOUT

FIRST RADIOBIOLOGICAL RESULTS

DOSIMETRY

: 0.208 ± 0.016β: 0.020 ± 0.003

FUTURE DEVELOPMENTS

TOP (Oncological Therapy with Protons) - IMPLART (Intensity Modulated Proton Linear Accelerator for RadioTherapy) project curried out by ENEA, ISS and IFO as the end-user, is based

on a compact pulsed 230 MeV proton LINAC designed for fully active scanning (3+1)D in intensity (instantaneous released dose), energy (depth) and transversal position (x-y). Peculiar

characteristics of the system are: modularity, pulsed operation naturally suited to IMPT, fast energy variation, high quality beam, high dose rate capability, reduced beam losses and

reduced neutron production along the accelerating sections. The TOP-IMPLART proton beams will also be used for in vivo” and “in vitro” radiobiological studies.

DOSE DELIVERY MONITOR OF THE TOP-IMPLART

PROTON THERAPY BEAM

A dose delivery monitor was specifically designed for the TOP

IMPLART beam characteristics. It will measure the beam

intensity profile, position and direction to monitor the fully active

3+1D (x, y, z and intensity) pulsed beam. The monitor system

consists of segmented ionization chambers and it is driven by

dedicated electronics.

Assembled chamber

prototype

First electron beam tests of the chamber prototype of the dose delivery monitor show good noise

characteristics and excellent beam profile measurements. Further and more accurate

characterization tests are in progress, while a new, consolidated version of the chamber and the

electronics is under development.

SCATTERING CHAMBER AND MULTISAMPLE HOLDER

Energy measurement of a proton beam after a

scattering process

The scattering process happens inside a scattering

chamber with a vacuum of P~ 10−3 Pa. Target and

detectors can be moved inside the chamber. The energy

of the scattered proton is measured by a Lithium drifted

Silicon detector with 5 mm of thickness. The angle is

determined by a mechanic positioning system of the

detector that uses a quadrature encoder with a resolution

better than 0,004 degrees.

0.01

0.1

1

0 2 4 6 8 10

SF 1

SF 2

SF 3

SF

Sur

vivi

ng F

ract

ion

Dose / Gy

CHO TOP protons (3 exps)

0.01

0.1

1

0 2 4 6 8 10

SF 1SF 2SF 3SF 4SF

Sur

vivi

ng F

ract

ion

Dose / Gy

V79 TOP protons (4 exps)

The dose-response curves for clonogenic survival were found

to be characterized by an initial shoulder (more pronunced in

V79 than in CHO cells) followed by a straight portion, that can

be well fitted by a linear-quadratic function of the dose. The

results on V79 cells, widely used in hadrontherapy

experiments, were found in good agreement with the previous

data obtained at LNL. Also the data obtained using CHO cells

were consistent with literature results (Tang et al., British

Journal of Cancer 1997). Experiments are planned with a

differernt proton energy to extend the radiobiological

characterization of the TOP-IMPLART proton beam.: 0.186 ± 0.019β: 0.090 ± 0.003

Dosimetry was carried out using GafChromic EBT3 films, calibrated at the INFN-LNL Laboratories with a

proton beam having the same energy, at the entrance of the EBT3 film, as the protons produced by the

TOP-IMPLART accelerator for these radiobiological experiments. (Vadrucci et al., accepted for

pubblication in Medical Physics)

Low energy Radiobiology Experiments: beam parameters

Energy Energy spread LET Fluence Pulse

CurrentPulse

DurationRepetition Frequency Dose Rate

5 MeV 0.1 MeV 7.7 keV/m 105÷106

protons/cm2 0.16 A 13 s 10 Hz 2 – 5 Gy/min

V79 (4 exps)

CHO (3 exps)

Dos

e to

MS2

0 (G

y)

netOD

Belli et al., International Journal of Radiation Biology 1999

Fig.1 Survival curves for V79 cells irradiated with X-rays and protons with different LET. Each data point represent the mean of at least seven independent experiments and the error bars denote one standard error of the mean.

: 0.208 ± 0.017 β: 0.020 ± 0.003

Table 2 Parameters obtained from the best fit od the s rvival curves

RBE-LET relationship for cell inactibation and mutation induced by low energy protons in V79 cells: further results at the LNL facilitymylar foil

protons

cell monolayer